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249500.9796Transmission of Mobile Colistin Resistance (mcr-1) by Duodenoscope. BACKGROUND: Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1-harboring bacteria in the United States. METHODS: A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. RESULTS: Two patients had highly related mcr-1-positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. Klebsiella pneumoniae and Escherichia coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. CONCLUSIONS: We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of a US Food and Drug Administration-cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings.201930204838
226110.9788Emergence of drug resistant bacteria at the Hajj: A systematic review. BACKGROUND: Hajj is the annual mass gathering of Muslims, and is a reservoir and potential source of bacterial transmission. The emergence of bacterial transmission, including multi-drug resistance (MDR) bacteria, during Hajj has not been systematically assessed. METHODS: Articles in Pubmed, Scopus, and Google scholar were identified using controlled words relating to antibiotic resistance (AR) at the Hajj from January 2002 to January 2017. Eligible studies were identified by two researchers. AR patterns of bacteria were obtained for each study. RESULTS: We included 31 publications involving pilgrims, Hajj workers or local patients attending hospitals in Mecca, Mina, and the Medina area. Most of these publications provided antibiotic susceptibility results. Ten of them used the PCR approach to identify AR genes. MRSA carriage was reported in pilgrims and food handlers at a rate of 20%. Low rates of vancomycin-resistant gram-positive bacteria were reported in pilgrims and patients. The prevalence of third-generation cephalosporin-resistant bacteria was common in the Hajj region. Across all studies, carbapenem-resistant bacteria were detected in fewer than 10% of E.coli isolates tested but up to 100% in K. pneumoniae and A. baumannii. Colistin-resistant Salmonella enterica, including mcr-1 colistin-resistant E.coli and K.pneumoniae were only detected in the pilgrim cohorts. CONCLUSION: This study provides an overview of the prevalence of MDR bacteria at the Hajj. Pilgrims are at high risk of AR bacterial transmission and may carry and transfer these bacteria when returning to their home countries. Thus, pilgrims should be instructed by health care practitioners about hygiene practices aiming at reducing traveler's diarrhea and limited use of antibiotics during travel in order to reduce the risk of MDR bacterial transmission.201728652197
147420.9787Simple, rapid, and cost-effective modified Carba NP test for carbapenemase detection among Gram-negative bacteria. PURPOSE: Detection of carbapenemases among Gram-negative bacteria (GNB) is important for both clinicians and infection control practitioners. The Clinical and Laboratory Standards Institute recommends Carba NP (CNP) as confirmatory test for carbapenemase production. The reagents required for CNP test are costly and hence the test cannot be performed on a routine basis. The present study evaluates modifications of CNP test for rapid detection of carbapenemases among GNB. MATERIALS AND METHODS: The GNB were screened for carbapenemase production using CNP, CarbAcineto NP (CANP), and modified CNP (mCNP) test. A multiplex polymerase chain reaction (PCR) was performed on all the carbapenem-resistant bacteria for carbapenemase genes. The results of three phenotypic tests were compared with PCR. RESULTS: A total of 765 gram negative bacteria were screened for carbapenem resistance. Carbapenem resistance was found in 144 GNB. The metallo-β-lactamases were most common carbapenemases followed by OXA-48-like enzymes. The CANP test was most sensitive (80.6%) for carbapenemases detection. The mCNP test was 62.1% sensitive for detection of carbapenemases. The mCNP, CNP, and CANP tests were equally sensitive (95%) for detection of NDM enzymes among Enterobacteriaceae. The mCNP test had poor sensitivity for detection of OXA-48-like enzymes. CONCLUSION: The mCNP test was rapid, cost-effective, and easily adoptable on routine basis. The early detection of carbapenemases using mCNP test will help in preventing the spread of multidrug-resistant organisms in the hospital settings.201728966495
957230.9782Diagnostic Evasion of Highly-Resistant Microorganisms: A Critical Factor in Nosocomial Outbreaks. Highly resistant microorganisms (HRMOs) may evade screening strategies used in routine diagnostics. Bacteria that have evolved to evade diagnostic tests may have a selective advantage in the nosocomial environment. Evasion of resistance detection can result from the following mechanisms: low-level expression of resistance genes not resulting in detectable resistance, slow growing variants, mimicry of wild-type-resistance, and resistance mechanisms that are only detected if induced by antibiotic pressure. We reviewed reports on hospital outbreaks in the Netherlands over the past 5 years. Remarkably, many outbreaks including major nation-wide outbreaks were caused by microorganisms able to evade resistance detection by diagnostic screening tests. We describe various examples of diagnostic evasion by several HRMOs and discuss this in a broad and international perspective. The epidemiology of hospital-associated bacteria may strongly be affected by diagnostic screening strategies. This may result in an increasing reservoir of resistance genes in hospital populations that is unnoticed. The resistance elements may horizontally transfer to hosts with systems for high-level expression, resulting in a clinically significant resistance problem. We advise to communicate the identification of HRMOs that evade diagnostics within national and regional networks. Such signaling networks may prevent inter-hospital outbreaks, and allow collaborative development of adapted diagnostic tests.201729163416
979940.9781Microbiology and drug resistance mechanisms of fully resistant pathogens. The acquisition of vancomycin resistance by Gram-positive bacteria and carbapenem resistance by Gram-negative bacteria has rendered some hospital-acquired pathogens impossible to treat. The resistance mechanisms employed are sophisticated and very difficult to overcome. Unless alternative treatment regimes are initiated soon, our inability to treat totally resistant bacteria will halt other developments in medicine. In the community, Gram-positive bacteria responsible for pneumonia could become totally resistant leading to increased mortality from this common infection, which would have a more immediate impact on our current lifestyles.200415451497
907550.9780CamPype: an open-source workflow for automated bacterial whole-genome sequencing analysis focused on Campylobacter. BACKGROUND: The rapid expansion of Whole-Genome Sequencing has revolutionized the fields of clinical and food microbiology. However, its implementation as a routine laboratory technique remains challenging due to the growth of data at a faster rate than can be effectively analyzed and critical gaps in bioinformatics knowledge. RESULTS: To address both issues, CamPype was developed as a new bioinformatics workflow for the genomics analysis of sequencing data of bacteria, especially Campylobacter, which is the main cause of gastroenteritis worldwide making a negative impact on the economy of the public health systems. CamPype allows fully customization of stages to run and tools to use, including read quality control filtering, read contamination, reads extension and assembly, bacterial typing, genome annotation, searching for antibiotic resistance genes, virulence genes and plasmids, pangenome construction and identification of nucleotide variants. All results are processed and resumed in an interactive HTML report for best data visualization and interpretation. CONCLUSIONS: The minimal user intervention of CamPype makes of this workflow an attractive resource for microbiology laboratories with no expertise in bioinformatics as a first line method for bacterial typing and epidemiological analyses, that would help to reduce the costs of disease outbreaks, or for comparative genomic analyses. CamPype is publicly available at https://github.com/JoseBarbero/CamPype .202337474912
980860.9779Understanding Recent Developments in Colistin Resistance: Mechanisms, Clinical Implications, and Future Perspectives. Colistin resistance, driven by chromosomal mutations and the spread of plasmid-mediated MCR genes, has emerged as a critical challenge in combating multidrug-resistant Gram-negative bacteria. This resistance compromises the efficacy of colistin, leading to higher treatment failure rates, prolonged hospitalizations, and increased mortality. Recent studies have highlighted key mechanisms, including lipid A modifications, that enable bacteria to evade colistin's effects. The global spread of MCR genes exacerbates the issue, underlining the need for improved diagnostics and rapid detection of resistant strains to prevent adverse patient outcomes. To combat this growing threat, a multifaceted approach is essential, involving enhanced antimicrobial stewardship, stricter infection control measures, and continued research into alternative therapies and diagnostic methods. Collaborative efforts from researchers, healthcare providers, policymakers, and the pharmaceutical industry are crucial to preserving colistin's effectiveness and mitigating the broader impact on public health.202541148650
485470.9779Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria. Carbapenem resistance in gram-negative bacteria has caused a global epidemic that continues to grow. Although carbapenemase-producing Enterobacteriaceae have received the most attention because resistance was first reported in these pathogens in the early 1990s, there is increased awareness of the impact of carbapenem-resistant nonfermenting gram-negative bacteria, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Moreover, evaluating the problem of carbapenem resistance requires the consideration of both carbapenemase-producing bacteria as well as bacteria with other carbapenem resistance mechanisms. Advances in rapid diagnostic tests to improve the detection of carbapenem resistance and the use of large, population-based datasets to capture a greater proportion of carbapenem-resistant organisms can help us gain a better understanding of this urgent threat and enable physicians to select the most appropriate antibiotics.201931724045
979080.9779Emerging antibiotic resistance: carbapenemase-producing enterobacteria. Bad new bugs, still no new drugs. Antimicrobial resistance (AMR) is a global health security threat requiring actions across government sectors and society. Many factors are involved in this phenomenon, being overuse of antibiotics, incorrect antibiotic prophylaxis, and use of antibiotics for zootechnic reasons the main causes of the increasing rate of multi-drug resistant (MDR) bacteria. The impact of resistance to antimicrobials is an important threat due also to the emergence of MDR Gram-negative bacteria resistant to carbapenems, and the lack of the research for new active molecules. The production of extended spectrum beta-lactamase enzymes has been the first threatening mechanism for Gram-negative resistance to antibiotics, which prompted the development of new classes of antibiotics such as carbapenems. Unfortunately, resistance to carbapenems developed because of multiple mechanisms including efflux pumps, porin mutations and enzyme production, being the latter particularly relevant in terms of diffusion due to the genes located within plasmids that drive their horizontal diffusion. In this scenario, antimicrobial stewardship programs (ASP) are a mandatory resource in fighting the resistance spread. The reduction of total amount of antibiotics administration in the hospital setting and guiding prescribers in the correct administration of antibiotics for the smallest period possible, at the correct dosage, can be defined as the first goals of an ASP. Anyway, in an efficacious ASP, apart from antibiotic administration, efforts must been made in ensuring the lowest probability of spreading of MDR by efficacious measures of isolation of carriers, and by offering tools for a rapid diagnosis of viral infections avoiding the administration of unnecessary antibiotics. A continuous audit of the ASP programs and a correct assessment of the allergy to drugs such as penicillin have to complete the program. Currently, only a few options are available for patients with an infection sustained by Gram-negative MDR bacteria. All the options actually available are based on the administration of colystin, an old drug whose real efficacy is reduced due to its relevant toxicity, or on the administration of recently proposed drugs such as ceftolozane-tazobactam, ceftazidime-avibactam and meropenem-vaborbactam. All these new drugs do not have a novel mechanism of action and have limited spectrum in term of activity against MDR bacteria. In conclusion, antimicrobial resistance is a global emergence and AMP is the most powerful tool actually available. Few limited options are available to treat infections due to Carbapenem Resistant Enterobacteria. Antimicrobial molecules with true novel mechanism of action are needed to win the fight against antimicrobial resistance.201931846984
979690.9779Bacteriophage therapy to combat MDR non-fermenting Gram-negative bacteria causing nosocomial infections: recent progress and challenges. Clinicians face significant challenges in managing nosocomial infections, primarily due to antimicrobial resistance in multidrug-resistant bacteria. Regardless of the availability of a wide range of antimicrobials in the market, resistance is escalating rampantly with every passing day, which has become a global concern. Hence, it is essential to discover new and more efficient techniques to eliminate pathogens from healthcare settings. Along with eliminating pathogenic bacteria, mitigating their antimicrobial resistance with novel methods is very essential. Recently, bacteriophages have re-emerged as a promising therapeutic alternative to treat serious infections caused by bacterial pathogens. Bacteriophages were discovered for the first time a century ago, but their usage has recently regained more attention in treating bacterial pathogens. Bacteriophages also help in mitigating the worldwide problem of antibiotic resistance, particularly augmented by Gram-negative bacteria. This review discussed the advancements in the usage of bacteriophages in combating the antimicrobial resistance of multidrug-resistant Gram-negative bacteria, with a prime focus on Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cepacia complex (Bcc), which are renowned non-fermenting Gram-negative bacteria (NFGNB) pathogens. Additionally, the effects of single phage, phage cocktails, and combination therapy with antibiotics on bacterial biofilms and polymicrobial biofilms are also discussed.202540478338
9584100.9779Using bacteria to express and display anti-parasite molecules in mosquitoes: current and future strategies. Vector-borne diseases impose enormous health and economical burdens throughout the world. Unfortunately, as insecticide and drug resistance spread, these burdens will increase unless new control measures are developed. Genetically modifying vectors to be incapable of transmitting parasites is one possible control strategy and much progress has been made towards this goal. Numerous effector molecules have been identified that interfere with parasite development in its insect vectors, and techniques for transforming the vectors with genes encoding these molecules have been established. While the ability to generate refractory vectors is close at hand, a mechanism for replacing a wild vector population with a refractory one remains elusive. This review examines the feasibility of using bacteria to deliver the anti-parasitic effector molecules to wild vector populations. The first half briefly examines paratransgenic approaches currently being tested in both the triatomine bug and tsetse fly. The second half explores the possibility of using midgut bacteria to control malaria transmission by Anopheles mosquitoes.200515894187
9794110.9779Antibiotic resistance in developing countries. During the past decade there have been major changes in the susceptibility of bacteria that cause various infections. Resistance to anti-infective agents, including antibiotics, is worldwide, both in developed and developing countries. Almost all bacterial species can develop resistance to anti-infective agents and resistance can readily be transferred among bacteria by transmissible elements (plasmids). Measures to prevent the emergence of resistance must be implemented urgently. A multiplicity of factors drive antibiotic resistance and solutions require the collaboration of governmental agencies, pharmaceutical companies, healthcare providers and consumers. Knowledge of resistance patterns and of the ways by which resistance is overcome is vital to the future of antimicrobial chemotherapy.200111434528
9789120.9778Nosocomial antibiotic resistance in multiple gram-negative species: experience at one hospital with squeezing the resistance balloon at multiple sites. Increased use of antibiotics has led to the isolation of multidrug-resistant bacteria, especially in intensive care units and long-term care facilities. Resistance in specific gram-negative bacteria, including Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, is of great concern, because a growing number of reports have documented mechanisms whereby these microorganisms have become resistant to all available antibacterial agents used in therapy. Reduction in the selection of these multidrug-resistant bacteria can be accomplished by a combination of several strategies. These include having an understanding of the genetics of both innate and acquired characteristics of bacteria; knowing resistance potentials for specific antibacterials; monitoring resistance trends in bacteria designated as problematic organisms within a particular institution on a routine basis; modifying antibiotic formularies when and where needed; creating institutional education programs; and enforcing strict infection-control practices. Strategies appropriate for primary prevention of nosocomial resistance may differ from those required for control of existing epidemic or endemic resistance.200211797177
9393130.9778Self-limiting paratransgenesis. Presently, the principal tools to combat malaria are restricted to killing the parasite in infected people and killing the mosquito vector to thwart transmission. While successful, these approaches are losing effectiveness in view of parasite resistance to drugs and mosquito resistance to insecticides. Clearly, new approaches to fight this deadly disease need to be developed. Recently, one such approach-engineering mosquito resident bacteria to secrete anti-parasite compounds-has proven in the laboratory to be highly effective. However, implementation of this strategy requires approval from regulators as it involves introduction of recombinant bacteria into the field. A frequent argument by regulators is that if something unexpectedly goes wrong after release, there must be a recall mechanism. This report addresses this concern. Previously we have shown that a Serratia bacterium isolated from a mosquito ovary is able to spread through mosquito populations and is amenable to be engineered to secrete anti-plasmodial compounds. We have introduced a plasmid into this bacterium that carries a fluorescent protein gene and show that when cultured in the laboratory, the plasmid is completely lost in about 130 bacterial generations. Importantly, when these bacteria were introduced into mosquitoes, the bacteria were transmitted from one generation to the next, but the plasmid was lost after three mosquito generations, rendering the bacteria non-recombinant (wild type). Furthermore, no evidence was obtained for horizontal transfer of the plasmid to other bacteria either in culture or in the mosquito. Prior to release, it is imperative to demonstrate that the genes that thwart parasite development in the mosquito are safe to the environment. This report describes a methodology to safely achieve this goal, utilizing transient expression from a plasmid that is gradually lost, returning the bacterium to wild type status.202032810151
4896140.9778The changing ecology of bacterial infections in children. There is continued change in the organisms involved in commonly encountered infections. Although the major organisms have changed less in pediatric than in medical or surgical infections, the advances in neonatology and the chemotherapy of leukemia have resulted in cases in which infection with once uncommon organisms is now commonplace. Perhaps more disheartening has been the increasing resistance of bacteria to antibiotics. Since resistance patterns are so much a reflection of antibiotic usage patterns in an institution, each pediatrician must be aware of the species of bacteria and the resistance patterns of the bacteria isolated in his hospital, particularly in neonatal, intensive care, and burn areas where there is the highest use of antibiotics. Close interaction of pediatrician, diagnostic microbiology laboratory, and hospital epidemiologist can provide early clues to possible bacteria involved in infection, as well as suspected antibiotic resistance patterns.19761253540
2518150.9778Plasmids Carrying Antimicrobial Resistance Genes in Gram-Negative Bacteria. Gram-negative bacteria are prevalent pathogens associated with hospital-acquired infections (HAI) that are a major challenge for patient safety, especially in intensive care units [...].202236014095
5167160.9778Decreased Antimicrobial Resistance Gene Richness Following Fecal Microbiota, Live-jslm (REBYOTA®) Administration: Post Hoc Analysis of PUNCH CD3. BACKGROUND: The human gastrointestinal microbiome helps maintain vital functions related to overall health, including resistance to pathogen colonization. Disruption of the microbiome, leading to loss of colonization resistance, can be caused by multiple factors, including antimicrobial use. The loss of colonization resistance may lead to establishment or proliferation of opportunistic bacteria that carry genes associated with antimicrobial resistance, potentially increasing the risk of infection by such antimicrobial-resistant bacteria. A potential approach to mitigating this risk involves restoration of healthier microbiota and pathogen colonization resistance. METHODS: A metagenomic sequencing method was used to conduct a post hoc analysis of antibiotic resistance gene richness among fecal samples from participants administered fecal microbiota, live-jslm (REBYOTA; abbreviated as RBL) or placebo in the PUNCH CD3 study (NCT03244644) for the prevention of recurrent Clostridioides difficile infection. RESULTS: At baseline, participants had higher antibiotic resistance gene richness than a representative healthy cohort. Over time, RBL responders had lower antibiotic resistance gene richness at the class, group, and mechanism levels as compared with placebo responders. These differences were evident as early as 1 week after administration and sustained for at least 6 months. RBL responders also had decreased richness of antibiotic resistance genes deemed high risk based on designated bacterial public health threats. CONCLUSIONS: These data support a model in which microbiota-based products, including RBL, may reduce antibiotic resistance gene richness, thereby possibly reducing the risk of antimicrobial-resistant organism infection. TRIAL REGISTRATION: NCT03244644 (https://clinicaltrials.gov/study/NCT03244644; 9 August 2017).202540672762
2516170.9778Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention - a comprehensive review. Intensive care units (ICUs) are specialized environments dedicated to the management of critically ill patients, who are particularly susceptible to drug-resistant bacteria. Among these, carbapenem-resistant Gram-negative bacteria (CR-GNB) pose a significant threat endangering the lives of ICU patients. Carbapenemase production is a key resistance mechanism in CR-GNB, with the transfer of resistance genes contributing to the extensive emergence of antimicrobial resistance (AMR). CR-GNB infections are widespread in ICUs, highlighting an urgent need for prevention and control measures to reduce mortality rates associated with CR-GNB transmission or infection. This review provides an overview of key aspects surrounding CR-GNB within ICUs. We examine the mechanisms of bacterial drug resistance, the resistance genes that frequently occur with CR-GNB infections in ICU, and the therapeutic options against carbapenemase genotypes. Additionally, we highlight crucial preventive measures to impede the transmission and spread of CR-GNB within ICUs, along with reviewing the advances made in the field of clinical predictive modeling research, which hold excellent potential for practical application.202438601497
9560180.9778The History of Colistin Resistance Mechanisms in Bacteria: Progress and Challenges. Since 2015, the discovery of colistin resistance genes has been limited to the characterization of new mobile colistin resistance (mcr) gene variants. However, given the complexity of the mechanisms involved, there are many colistin-resistant bacterial strains whose mechanism remains unknown and whose exploitation requires complementary technologies. In this review, through the history of colistin, we underline the methods used over the last decades, both old and recent, to facilitate the discovery of the main colistin resistance mechanisms and how new technological approaches may help to improve the rapid and efficient exploration of new target genes. To accomplish this, a systematic search was carried out via PubMed and Google Scholar on published data concerning polymyxin resistance from 1950 to 2020 using terms most related to colistin. This review first explores the history of the discovery of the mechanisms of action and resistance to colistin, based on the technologies deployed. Then we focus on the most advanced technologies used, such as MALDI-TOF-MS, high throughput sequencing or the genetic toolbox. Finally, we outline promising new approaches, such as omics tools and CRISPR-Cas9, as well as the challenges they face. Much has been achieved since the discovery of polymyxins, through several innovative technologies. Nevertheless, colistin resistance mechanisms remains very complex.202133672663
4855190.9778Carbapenem-resistant enterobacteriaceae: an emerging problem in children. Antibiotic resistance among gram-negative bacteria has reached critical levels. The rise of carbapenem resistance in Enterobacteriaceae carrying additional resistance genes to multiple antibiotic classes has created a generation of organisms nearly resistant to all available therapy. Carbapenem-resistant Enterobacteriaceae (CRE) infections are known to be associated with significant morbidity and mortality, and these pathogens have now made their way to the most vulnerable populations, including children. This review provides a brief overview of CRE, with a focus on CRE infections in children, and highlights available data on the epidemiology, clinical characteristics, carbapenemase types, risk factors, treatment, and outcomes of these multi-drug resistant infections in the pediatric population.201222700827